Genetics

What are genes?

Genes are the part of a body cell that contains the biological information that parents pass to their children. Genes control the growth and development of cells. Genes are contained in DNA (deoxyribonucleic acid), a substance inside the center (nucleus) of cells that contains instructions for the development of the cell.

You inherit half of your genetic information from your mother and the other half from your father. Genes, alone or in combination, determine what features (genetic traits) a person inherits from his or her parents, such as blood type, hair color, eye color, and other characteristics, including risks of developing certain diseases. Certain changes in genes or chromosomes may cause defects in various body processes or functions.

What are chromosomes?

Many genes together make up larger structures within the cell called chromosomes. Each cell normally contains 23 pairs of chromosomes.¹

A human has 46 chromosomes (23 pairs). One chromosome from each pair comes from the mother, and one chromosome from each pair comes from the father. One of the 23 pairs determines your sex. The sex chromosomes are called X and Y.

• For a child to be female, she must inherit an X chromosome from each parent (XX).
• For a child to be male, he must inherit an X chromosome from his mother and a Y chromosome from his father (XY).

Some genetic disorders are caused when all or part of a chromosome is missing, or when an extra chromosome or chromosome fragment is present.

What is genetic testing?

Genetic testing examines a DNA sample for gene changes, or it may analyze the number, arrangement, and characteristics of the chromosomes. Testing may be performed on samples of blood, semen, urine, saliva, stool, body tissues, bone, or hair.

Should I have genetic testing?

You may choose to have genetic testing if you are concerned that you have an increased risk of having or getting a disease that has a genetic cause. The information you obtain from the tests may help you make decisions about your life. For example:

• If tests determine that you have an increased risk for passing on a disease to your child, you may choose to have more genetic testing while you are pregnant (prenatal testing). Or you may decide to adopt a child.
• If tests determine that you have an increased risk for developing a disease such as breast cancer, you may make decisions that help lower your risk for breast cancer.
• You may feel reassured if the tests are normal.

You may decide to have a genetic test during pregnancy to determine whether your fetus has a disorder, such as Down syndrome. Information obtained from the test can help you decide how to manage your pregnancy.

Genetic testing can be used to determine the identity of a child's father (paternity). It can also be used in crime scene investigation.

What are the main types of genetic testing?

There are five main types of genetic testing:

• Carrier identification determines whether people who have a family history of a specific disease or who are in a group that has an increased chance for that disease are likely to pass on that disease to their children. Information obtained from this type of testing can help guide a couple as they make decisions about pregnancy.
• Prenatal testing determines whether a fetus has a disorder, such as Down syndrome. Information gained from this type of testing can help guide decisions about how to manage a pregnancy, including the decision about whether to end the pregnancy.
• Newborn screening checks for various metabolic diseases, such as phenylketonuria (PKU). Information obtained from newborn screening can help guide medical treatment to ensure the best possible outcome for the baby.
• Late-onset disease testing determines whether you carry a genetic change that increases your risk for developing a disease, such as breast cancer or Huntington's disease, later in life. This might be of interest if you have a relative with the disease. Information obtained from this type of testing can help you make decisions about preventing or managing the disease.
• Genetic identification (DNA fingerprinting) can be used to determine paternity, help solve crimes, and identify a body. DNA fingerprinting is more accurate than dental records, blood type, or traditional fingerprints.

What are the risks of genetic testing?

The information obtained from genetic testing can affect your life and the lives of your family members. The issues involved include:

• Psychological. The emotions you may experience if you learn that you have a greater chance of having or passing on a serious disease can cause you to feel anxious or depressed. This may also affect your relationship with your partner or other family members. Genetic counseling is recommended prior to genetic testing.
• Medical. A person who tests positive for a disease-specific gene may decide to use preventive or treatment options to reduce the impact or severity of the disease. Although many treatment options are proven effective, others may be potentially dangerous or of unproven value.
• Privacy. Because genetic testing is expensive, few people are able to afford it without assistance from their insurance companies. Many people worry that genetic information released to insurance companies may affect future employment options or insurance availability. Although many people are fearful of this, it rarely happens.

Every person carries two copies of most genes (one copy from the mother and one from the father). A carrier is a person who has a change in one copy of a gene. The carrier does not have the genetic disease related to the abnormal gene. A carrier can pass this abnormal gene to a child. Carrier identification is a type of genetic testing that can determine whether people who have a family history of a specific disease, or who are in a group that has a greater chance of having a disease, are likely to pass that disease to their children. Information from this type of testing can guide a couple's decision about having children.

For many genetic disorders, carrier testing can help determine how likely it is that a child will have the disease:

• If both parents carry the abnormal gene, there is a 1-in-4 (25%) chance that their child will have the disease and a 2-in-4 (50%) chance that their child will be a carrier of the disease (but will not have it). There is also a 1-in-4 (25%) chance that the child will not get the abnormal gene and so will not have the disease nor be a carrier.
• If only one parent carries the abnormal gene, the child has a 1-in-2 (50%) chance of being a carrier but almost no chance that he or she will have the disease.

Examples of screening tests to identify carriers for specific genetic disorders include:

• Cystic fibrosis carrier screening. These tests identify the most common changes or mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. Many couples planning to become pregnant have this type of screening to determine whether either or both of them carry a defective CFTR gene.
• Sickle cell test. This test is used to identify someone with sickle cell trait. A person who has sickle cell trait may have a child with sickle cell disease if his or her partner is also a carrier.
• Tay-Sachs test. This test is used to identify Tay-Sachs carriers. People of Ashkenazi Jewish or French-Canadian descent who have a family history of Tay-Sachs disease or who live in a community or population with a high prevalence of Tay-Sachs disease may choose to be tested to see if they are a Tay-Sachs carrier.

Genetic testing is used to determine whether a fetus has a disease or genetic abnormality such as Down syndrome or trisomy 18. Information obtained from this type of testing may help guide decisions during pregnancy.

Other tests are used for prenatal screening to determine whether a fetus has an increased risk for a genetic disease. These tests can help identify substances that might indicate a genetic disease. Examples of tests used for prenatal screening include:

• Triple screen test. This test measures levels of three substances in a pregnant woman's blood that indicate how likely it is that the fetus has Down syndrome, trisomy 18, or a neural tube defect.² The results of this test are combined with other information (pregnant woman's age, weight, race, and whether she has diabetes) to estimate the risk of Down syndrome in the fetus. Sometimes the tests indicate that a fetus is likely to have Down syndrome but the fetus is unaffected. This is called a false-positive result. Or sometimes screening tests do not find the condition when it is present. This is called a false-negative result. The substances measured in the triple screen test are:
  • Alpha-fetoprotein (AFP), a substance naturally produced by the liver of a fetus.
  • Human chorionic gonadotropin (hCG), a hormone produced by the placenta during pregnancy.
  • Estriol (uE3), a hormone produced by the placenta during pregnancy.
• Quad screen test. This adds another hormone (inhibin A) to the three substances tested for in the triple screen. The results of this test are combined with the pregnant woman's age, weight, race, and whether or not she has diabetes to help determine whether the fetus has a greater chance of having a condition such as trisomy 18, Down syndrome, or a neural tube defect. The results of a quad screen are generally more accurate than the results of a triple screen.
• Fetal ultrasound. This test uses reflected sound waves to produce a picture of the fetus, the placenta, and amniotic fluid. It is used to determine whether the fetus has a structural abnormality, such as a heart defect.

In some cases a combination of screening tests is done in the first trimester to look for Down syndrome or trisomy 18. This is sometimes called integrated screening. The screening test uses an ultrasound measurement of the thickness of the fetus's neck (nuchal fold or translucency) and the levels of hCG and a protein called pregnancy-associated plasma protein A (PAPP-A). The sensitivity of this screening test is about the same as that of the second-trimester maternal serum quad screening.³

If prenatal screening test results are abnormal, further genetic testing (karyotype) can be used to examine the size, shape, and number of chromosomes. A karyotype can be done on cells taken from the placenta (chorionic villus sampling) in the late first trimester or from the amniotic fluid (amniocentesis) in the second trimester. Extra, missing, or abnormal positions of chromosome pieces can cause problems with growth, development, and body functions.

Shortly after birth, a blood sample is taken from a newborn to screen for diseases such as phenylketonuria (PKU) and congenital hypothyroidism. This type of testing is important because treatment is available to improve the health of the child. Newborn screening is required in the United States, but states vary on which tests they offer.

Examples of tests used for newborn screening include:

• Phenylketonuria (PKU) screen, which measures the amount of phenylalanine in a baby's blood. Babies found to have PKU should be put on a special low-protein diet to prevent mental retardation.
• Newborn screening for cystic fibrosis. Levels of immunoreactive trypsinogen (IRT), a digestive enzyme, are measured from a blood sample. Abnormally high levels of IRT suggest cystic fibrosis, although further testing is needed to confirm the diagnosis.
• Hemoglobin test, which tests for types of hemoglobin in a baby's blood that may indicate sickle cell trait or sickle cell disease. Babies who have sickle cell disease need special medical care throughout their lives to treat the variety of problems that can be caused by the illness.

Other tests, such as newborn hearing tests, can tell whether a baby may need future hearing services or genetic testing. Approximately 50% of cases of newborn hearing loss are caused by genetic factors.⁴

This type of testing is done to determine whether you have a greater chance of having diseases that show up later in life (late-onset diseases). If you have a relative who has the disease, information obtained from these tests can help you make decisions about preventing or slowing the progress of the disease.

Genetic testing is used to identify the risk of late-onset diseases such as:

• Breast cancer and ovarian cancer (BRCA-1 and BRCA-2 testing).
• Familial adenomatous polyposis (FAP), which causes abnormal growths inside the colon and increases your risk of colorectal cancer.
• Huntington's disease, a rare disease that causes premature, severe deterioration of the brain.

Genetic testing used to determine the biological parent of a child is called DNA fingerprinting. It is also often used to help solve crimes by determining whether crime scene DNA evidence could be the same as the suspect's DNA.

DNA fingerprinting has been used to identify unknown people, such as military personnel killed in action or crime victims. DNA fingerprinting is more accurate for this purpose than dental records, blood type, traditional fingerprinting, or ID tags.

The information obtained from genetic testing can have a big impact on your life. Genetic counselors are trained to help you understand your risk of getting a disease related to genetics or of having a child with an inherited (genetic) disease, such as sickle cell disease, cystic fibrosis, or hemophilia. A genetic counselor can help you make well-informed decisions. Ask to have genetic counseling before making a decision about testing. Genetic counseling may involve:

• Discussing what problems an inherited disease may cause.
• Teaching you and your partner about how a specific disease is inherited or passed from you to your child.
• Discussing whether and how to test for an inherited disease before you become pregnant or before your child is born.
• Discussing the likelihood that you and your partner will have a child with an inherited disease, based on test results.

Genetic counseling can help you and your family:

• Understand medical facts, including what causes diseases, how a diagnosis is made, and what you may be able to do to help yourself manage a disease.
• Understand how your family history contributes to the development of a disease.
• Understand what you can do to help prevent a disease.
• Learn about caring for a family member who has a genetic disease, including getting referrals to specialists or joining support groups.

Genetic counselors are trained to help you and your family make informed decisions that are right for you. They are sensitive to physical and emotional aspects of these decisions. Your privacy and confidentiality are carefully protected.

Before making a decision about testing, you should clearly understand how the results of the test may affect your life. Consider how the test results may influence your decisions. If testing will not change any of your decisions, you may feel the test is not worth doing.

• Fetal genetic testing may detect a serious disease or disorder, such as Down syndrome, that will greatly impact your child's life and the lives of caregivers. A pregnant woman who is considering genetic testing may want to consider her ethical, social, and religious beliefs to help her determine the actions she would take if test results show a genetic disease.
• A genetic test result is sensitive information. Your confidentiality should be maintained, and the release of information should be limited to those who are authorized to receive it.
• Genetic testing can sometimes reveal unintended information, such as the identity of a child's father (paternity).
• The discovery of a genetic disease may affect your future ability to get work or some types of private insurance coverage. Although many people are fearful of this, it rarely happens.

Organizations

• Alpha-Fetoprotein (AFP) in Blood
• Amniocentesis
• Breast Cancer
• Breast Cancer (BRCA) Gene Test
• Chorionic Villus Sampling (CVS)
• Colorectal Cancer
• Cystic Fibrosis
• DNA Fingerprinting
• Down Syndrome
• Fetal Ultrasound
• Human Chorionic Gonadotropin (hCG)
• Karyotype Test
• Phenylketonuria (PKU)
• Phenylketonuria (PKU) Test
• Sickle Cell Disease
• Sickle Cell Test
• Tay-Sachs Disease
• Tay-Sachs Test

Citations

1. National Cancer Institute (2007). Cancer Genetics Overview (PDQ)—Health Professional Version. Available online: http://www.cancer.gov/cancertopics/pdq/genetics/overview/healthprofessional.

2. Fergal DM, D'Alton ME (2003). First-trimester sonographic screening for Down syndrome. Obstetrics and Gynecology, 102(5): 1066–1079.

3. American College of Obstetricians and Gynecologists (2004). ACOG issues position on first-trimester screening methods. Available online: http://www.acog.org/from_home/publications/press_releases/nr06-30-04.cfm.

4. Genetic Evaluation of Congenital Hearing Loss Expert Panel (2002; reaffirmed 2005). Genetics evaluation guidelines for the etiologic diagnosis of congenital hearing loss. Genetics in Medicine, 4(3): 162–171.

Other Works Consulted

• Elias ER, et al. (2007). Genetics and dysmorphology. In WW Hay et al., eds., Current Pediatric Diagnosis and Treatment, 18th ed., pp. 1011–1048. New York: McGraw-Hill.

• Pagana KD, Pagana TJ (2006). Mosby’s Manual of Diagnostic and Laboratory Tests, 3rd ed. St. Louis: Mosby.

• Pagon RA (2005). Genetic diagnosis and counseling. In DC Dale, DD Federman, eds., ACP Medicine, section 3, chap. 8. New York: WebMD.